Fatty acids as modulators of membrane functions: catecholamine-activated adenylate cyclase of the turkey erythrocyte.

Abstract

Activation of the adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1[ from turkey erythrocytes by isoproterenol decreased precipitously below 26 degrees. Certain unsaturated fatty acids enhanced the activation by isoproterenol up to 25-fold at reduced temperatures. The fatty acid also enhanced the formation of a persistent active state of the enzyme which was produced by preincubation with guanosine 5'-(beta,gamma-imino)triphosphate [Gpp(NH)p]. Once the enzyme had been activated by Gpp(NH)p plus isoproterenol the reaction rate was no longer as temperature sensitive and the fatty acid had little effect. The synthetic Gpp(NH)p apparently substituted for the natural GTP, which is known to play a regulatory role in the adenylate cyclase system. The findings suggest that the function of GTP which is mediated by the hormone is the temperature-sensitive event which is enhanced by the fatty acid. The use of free fatty acid to probe membrane-associated reactions in intact cells and in isolated membrane preparations is proposed.